Hydrochloric Acid → 2-Ethyl-5-phenyl-2H-pyrazole-3-carboxylic Acid Methoxy-methyl-amide

HRID 396405Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 396405
C(O[C:4]([C:6]1[N:7]([CH2:17][CH3:18])[N:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:10]=1)=[O:5])C.[OH-].[Na+].Cl.[CH3:22][O:23][NH:24][CH3:25].Cl.C(NCC)(C)C>CO.C(OCC)(=O)C.[Cl-].[Na+].O.CN(C=O)C>[CH3:22][O:23][N:24]([CH3:25])[C:4]([C:6]1[N:7]([CH2:17][CH3:18])[N:8]=[C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:10]=1)=[O:5]

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 88318IsopropylethylamineHCID 9878122Ethyl 1-Ethyl-3-phenyl-1H-pyrazole-5-carboxylate

Produkt 1

HCID 98783462-Ethyl-5-phenyl-2H-pyrazole-3-carboxylic Acid Methoxy-methyl-amideAusbeute 74,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×HCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

To a room temperature solution of the above-prepared 2-ethyl-5-phenyl-2H-pyrazole-3-carboxylic acid ethyl ester (165 mg, 675 μmoles) in MeOH (2 mL) was added aqueous NaOH (215 μL of a 10 N solution, 215 μmoles) under a nitrogen atmosphere. The resulting mixture was allowed to stir at room temperature overnight. The reaction was acidified with 6 N HCl, diluted with ethyl acetate and brine, and the phases were separated. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The crude acid was suspended in THF (2 mL), and carbonyldiimidazole was added (140 mg, 860 μmoles), and the mixture was stirred overnight at room temperature. The resulting acylimidazolide was treated with a preformed mixture of MeON(H)Me.HCl (140 mg, 1.43 mmole) and isopropylethylamine (250 μL, 1.43 mmoles) in DMF (1 mL) and the resulting mixture heated to 90° C. overnight. The reaction was then cooled to room temperature and diluted with ethyl acetate. The organic layer was washed with 1 M NaHSO4 (3×), brine, dried over Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (silica gel, hexanes/ethyl acetate gradient) provided the title compound (130 mg, 74% yield) as a thick oil.

Aufarbeitung

  1. customthe phases were separated
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. additioncarbonyldiimidazole was added (140 mg, 860 μmoles)
  6. stirringthe mixture was stirred overnight at room temperature
  7. temperaturethe resulting mixture heated to 90° C. overnight
  8. temperatureThe reaction was then cooled to room temperature
  9. washThe organic layer was washed with 1 M NaHSO4 (3×), brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1318ffa1532e4a7b867811451a2ae5cd
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06608087B1

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